The main objectives of this proposal are to determine the effects of immune complexes on the antibody response of mice to a vaccine prepared from Streptococcus pneumoniae R36a (Pn vaccine). The antigen in the immune complex is extracted from the cell wall of the Pn vaccine (PnC), and the antibody is, in most cases, an IgA myeloma protein that specifically binds PnC (TEPC-15). Using complexes formed between TEPC-15 and PnC, we have found that these complexes, when incubated with BALB/c spleen cells for 2 days, induce specific suppressor cells--that is, cells that are able to suppress the antibody plaque-forming cell (PFC) response of normal BALB/c spleen cells to the Pn vaccine, but not to other antigens such as sheep RBC. This proposal outlines experiments that will determine the cell type (eg. T, B, or macrophage) that mediates this suppression and the kinetics of its induction by immune complexes. In addition, we will determine whether the suppressor cell (SC) is specific for the antigen (PnC) or the antibody (i.e. idiotypic determinants in the V region of TEPC-15). We will also determine if the suppression is genetically restricted or determined by the isotype (heavy chain) of the antibody in the complex, as well as the sensitivity of the SC to a variety of metabolic inhibitors. Further experiments will characterize the effect of these SC in vivo and the direct effects of the complexes on antibody formation. Finally, we will determine whether the antigen/antibody complexes are bound to the surface of the SC or whether the SC have endogenous receptors for the antigen or antibody (idiotype) in the complex. The formation of immune complexes plays a role in a variety of human diseases including serum sickness, glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus, and thyroiditis. Elevated levels of circulating immune complexes have also been associated with a poor prognosis in patients with several cancers, including malignant melanoma, breast cancer, and lung cancer, as well as leukemia and Hodgkin's disease. Thus, the study of immune complexes is an important area of investigation.